Mucosal Nanoemulsion Allergy Vaccine Suppresses Alarmin Expression and Induces Bystander Suppression of Reactivity to Multiple Food Allergens.
Mucosal Nanoemulsion Allergy Vaccine Suppresses Alarmin Expression and Induces Bystander Suppression of Reactivity to Multiple Food Allergens.
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粘多糖纳米乳剂过敏疫苗抑制Alarmin表达并诱导旁观者对多种食物过敏原的反应性抑制。
DOI：
10.3389/fimmu.2021.599296
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发表时间：
2021
影响因子：
7.3
通讯作者：
O'Konek JJ
中科院分区：
文献类型：
--
作者：
Farazuddin M;Landers JJ;Janczak KW;Lindsey HK;Finkelman FD;Baker JR Jr;O'Konek JJ
我们已经证明，鼻内免疫疗法与过敏原配制在纳米乳液（NE）粘膜佐剂抑制Th 2/IgE介导的过敏反应，并保护从过敏原的挑战，在鼠食物过敏模型。这种疗法所赋予的保护与过敏原特异性Th 2细胞免疫的强烈抑制和Th 1细胞因子的增加有关。在这里，我们将这些研究扩展到检查NE过敏原免疫小鼠致敏多种食物的效果。小鼠对鸡蛋和花生过敏，然后接受用这些过敏原中的一种或两种配制的NE疫苗。然后用鸡蛋或花生对动物进行经口攻击，以评估反应性。用含有鸡蛋和花生的NE制剂进行免疫接种后，用任一种过敏原进行口服过敏原攻击后，反应性显著降低。有趣的是，接受仅含花生的疫苗的小鼠对鸡蛋的反应性也有所降低。尽管持续存在过敏原特异性IgE，但仍实现了对口服过敏原攻击的保护，并且与Th 2极化免疫应答、alarmins和2型先天淋巴细胞（ILC 2）的强烈抑制相关。NE诱导的旁观者反应性抑制需要IFN-γ和NE疫苗中过敏原的存在。这些结果表明，对食物过敏原的过敏反应可以使用过敏原特异性免疫疗法来抑制，而不必消除过敏原特异性IgE，并表明调节对一种过敏原的Th 2免疫可能诱导旁观者效应，该效应通过诱导IFN-γ和抑制肠道中的alarmin来抑制对其他过敏原的反应性。此外，这些数据表明，单一食物过敏原的NE疫苗可能导致对多种食物过敏反应的全面抑制。
We have demonstrated that intranasal immunotherapy with allergens formulated in a nanoemulsion (NE) mucosal adjuvant suppresses Th2/IgE-mediated allergic responses and protects from allergen challenge in murine food allergy models. Protection conferred by this therapy is associated with strong suppression of allergen specific Th2 cellular immunity and increased Th1 cytokines. Here we extend these studies to examine the effect of NE-allergen immunization in mice sensitized to multiple foods. Mice were sensitized to both egg and peanut and then received NE vaccine formulated with either one or both of these allergens. The animals were then subjected to oral challenges with either egg or peanut to assess reactivity. Immunization with NE formulations containing both egg and peanut markedly reduced reactivity after oral allergen challenge with either allergen. Interestingly, mice that received the vaccine containing only peanut also had reduced reactivity to challenge with egg. Protection from oral allergen challenge was achieved despite the persistence of allergen-specific IgE and was associated with strong suppression of both Th2-polarized immune responses, alarmins and type 2 innate lymphoid cells (ILC2). NE-induced bystander suppression of reactivity required IFN-γ and the presence of an allergen in the NE vaccine. These results demonstrate that anaphylactic reactions to food allergens can be suppressed using allergen-specific immunotherapy without having to eliminate allergen-specific IgE and suggests that modulation of Th2 immunity towards one allergen may induce bystander effects that suppress reactivity to other allergens through the induction of IFN-γ and suppression of alarmins in the intestine. In addition, these data suggest that a NE vaccine for a single food allergen may lead to a global suppression of allergic responses to multiple foods.
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影响因子：
4.9
作者：
Dunkin D;Berin MC;Mondoulet L;Tobar S;Yeretssian G;Tordesillas L;Iuga A;Larcher T;Gillespie V;Benhamou PH;Colombel JF;Sampson HA
通讯作者：
Sampson HA
影响因子：
4.4
作者：
Eisenbarth, SC;Zhadkevich, A;Bottomly, K
通讯作者：
Bottomly, K
DOI：
10.1056/nejmoa1200435
发表时间：
2012-07-19
期刊：
The New England journal of medicine
影响因子：
--
作者：
Burks AW;Jones SM;Wood RA;Fleischer DM;Sicherer SH;Lindblad RW;Stablein D;Henning AK;Vickery BP;Liu AH;Scurlock AM;Shreffler WG;Plaut M;Sampson HA;Consortium of Food Allergy Research (CoFAR)
通讯作者：
Consortium of Food Allergy Research (CoFAR)
影响因子：
14.2
作者：
Hussain, Maryam;Borcard, Loic;Noti, Mario
通讯作者：
Noti, Mario
影响因子：
14.2
作者：
Akdis, Muebeccel;Akdis, Cezmi A.
通讯作者：
Akdis, Cezmi A.